Fluconazole Interactions

Fluconazole inhibits CYP2C9, the main enzyme that clears warfarin, so it can sharply raise warfarin's blood-thinning effect within a few days of starting, even after a single antifungal dose. Case reports document this combination causing serious and sometimes fatal bleeding.

Fluconazole is a moderate inhibitor of the liver enzyme CYP3A4, and grapefruit irreversibly inhibits intestinal CYP3A4. Their effects overlap on the same enzyme. On their own the pair rarely causes a problem, but together they can further slow the clearance of a third medication that also depends on CYP3A4, allowing its blood levels to rise.